维生素A、维生素D水平与柯萨奇病毒A6型手足口病重症化的关联性研究

Association of Vitamin A and Vitamin D levels with severity of Coxsackie virus A6 induced hand,foot and mouth disease

目的探讨维生素A、维生素D与手足口病(HFMD)发病、病情及其与抗病毒免疫指标α干扰素(INF-α)之间的关系,探讨维生素A、维生素D在HFMD中的作用。方法选取西安市儿童医院2017年1月至2018年12月收治住院的柯萨奇病毒A6(CA6)型HFMD 305例为病例组,选择同期于西安市儿童医院儿童保健科体检的与病例组患儿性别、年龄相匹配的健康儿童100例为健康对照组。采用高效液相色谱法检测血清维生素A水平,酶联免疫吸附试验检测维生素D和IFN-α水平,分析维生素A、维生素D水平与HFMD重症化的相关性。结果CA6型HFMD患儿血清维生素A[(0.96±0.39)mg/mol]、维生素D[(42.14±15.13)μg/L]水平均低于健康对照组[维生素A(1.26±0.29)mg/mol、维生素D(49.63±8.86)μg/L],差异均有统计学意义(均P<0.05)。Logistic多因素回归分析显示,白细胞计数(WBC)>15×10^9/L、血糖>8.3 mmol/L、维生素A水平和维生素D水平降低均为CA6型HFMD重症化的危险因素(OR=2.303、4.622、7.346、5.211,均P<0.05)。受试者工作特征曲线分析显示,当维生素A为0.725 mg/mol时约登指数最大,该值对应的敏感性为82.0%,特异性为64.8%。当维生素D为32.88μg/L时约登指数最大,该值对应的敏感性为84.5%,特异性为61.9%。CA6型HFMD患儿血清IFN-α水平[(84.44±26.28)ng/L]高于健康对照组[(36.58±14.39)ng/L],差异有统计学意义(P<0.05)。重症HFMD患儿血清IFN-α水平[(71.48±18.34)ng/L]显著低于普通型患儿[(91.25±27.27)ng/L],差异有统计学意义(P<0.05)。相关分析显示,CA6型HFMD患儿血清IFN-α水平与维生素A、维生素D水平呈正相关(r=0.783、0.239,均P<0.001)。结论HFMD患儿血清维生素A、维生素D总体水平降低;WBC>15×10^9/L、血糖>8.3 mmol/L、维生素A水平和维生素D水平降低均与HFMD相关;血清IFN-α水平与维生素A、维生素D水平呈正相关,维生素A、维生素D缺乏是HFMD感染重症化的预警因素之一。

Objective To explore the relationship of Vitamin A and Vitamin D with the incidence and severity of hand, foot and mouth disease(HFMD) as well as with the anti-viral immune index interferon-α(INF-α), and to investigate the role of Vitamin A and Vitamin D in HFMD.Methods A total of 305 children with Coxsackie virus A6(CA6) HFMD admitted at Xi′an Children′s Hospital from January 2017 to December 2018 were enrolled in the study.One hundred healthy children whose gender and age matched with those of children in the case group were selected as the healthy control group.Serum Vitamin A levels were detected by high performance liquid chromatography.Enzyme-linked immunosorbent assay was used to detect the levels of Vitamin D and IFN-α, and the correlation of the levels of Vitamin A and Vitamin D with the severity of HFMD was analyzed.Results The levels of serum Vitamin A[(0.96±0.39) mg/mol] and Vitamin D [(42.14±15.13) μg/L] in patients with CA6 HFMD were lower than those of the healthy control group[(1.26±0.29) mg/mol, (49.63±8.86) μg/L], and the differences were statistically significant(all P<0.05). Logistic multivariate regression analysis showed that WBC>15×10^9/L, blood sugar>8.3 mmol/L, the deficiency of Vitamin A level and Vitamin D level were all risk factors for severe CA6 HFMD in children(OR=2.303, 4.622, 7.346, 5.211;all P<0.05). According to the receiver operating characteristic curve analysis, the Youden index was the largest at a Vitamin A level of 0.725 mg/mol, and the corresponding sensitivity and specificity were 82.0% and 64.8%, respectively.When Vitamin D level was 32.88 μg/L, the Youden index was the highest, and the sensitivity and specificity were 84.5% and 61.9%, respectively.The serum IFN-α concentration of patients with CA6 HFMD [(84.44±26.28) ng/L] was higher than that of the healthy control group [(36.58±14.39) ng/L], and the difference was statistically significant(P<0.05). In addition, the serum IFN-α concentration in severe HFMD children [(71.48±18.34) ng/L] was significantly lower than that in the common HFMD children [(91.25±27.27) ng/L], and the difference was statistically significant(P<0.05). The results of correlation analysis showed that serum IFN-α concentration is positively correlated with Vitamin A and Vitamin D levels (r=0.783, 0.239;all P<0.001).Conclusions The levels of serum Vitamin A and Vitamin D decreased in children with HFMD.WBC>15×10^9/L, blood sugar>8.3 mmol/L, the deficiency of Vitamin A level and Vitamin D level are related to severe HFMD.The se-rum IFN-α concentration is positively correlated with the levels of Vitamin A and Vitamin D. The deficiency of Vitamin A and Vitamin D is one of the early warning factors of severe HFMD.